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Despite the clinical benefits and safety profile of primary percutaneous coronary intervention (PCI), the health care system in the UK has been slow to adopt this strategy as first line management for ST segment elevation myocardial infarction. The cost implications of a 24 hour a day, seven days per week primary PCI service and the absence of an existing efficient working model within the National Health Service (NHS) framework are two of the major deterrents for provision of such a service. The existent cost effectiveness data for primary PCI is critically reviewed, with particular reference to the NHS.

Background: Patients with diabetes have an increased incidence and severity of ischemic heart disease, which leads to an increased requirement for coronary revascularization. Comparative information regarding mode of revascularization--coronary artery bypass graft surgery surgery (CABG) or percutaneous coronary intervention (PCI)--is limited, mainly confined to a subanalysis of the Bypass Angioplasty Revascularization (BARI) trial, suggesting a mortality benefit of CABG over PCI. No prospective trial has specifically compared these modes of revascularization in patients with diabetes., Objective: The Coronary Artery Revascularisation in Diabetes (CARDia) trial is designed to address the hypothesis that optimal PCI is not inferior to modern CABG as a revascularization strategy for diabetics with multivessel or complex single-vessel coronary disease. The primary end point is a composite of death, nonfatal myocardial infarction, and cerebrovascular accident at 1 year., Method: A total of 600 patients with diabetes are to be randomized to either PCI or CABG, with few protocol restrictions on operative techniques or use of new technology. This gives a power of 80% to detect non-inferiority of PCI assuming that the PCI 1-year event rate is 9%. A cardiac surgeon and a cardiologist must agree that a patient is suitable for revascularization by either technique prior to recruitment into the study. Twenty-one centers in the United Kingdom and Ireland are recruiting patients. Data on cost effectiveness, quality of life, and neurocognitive function are being collected. Long-term (3-5 year) follow-up data will also be collected.

There are over 1.3 million known diabetic patients in the UK and a similar number who have the disease undiagnosed. Over 90% have non-insulin dependent diabetes mellitus usually characterised by insulin resistance and adult onset. Over half of all diabetic patients die of coronary disease and account for over a fifth of percutaneous coronary intervention (PCI) revascularisation procedures. Despite recent therapeutic advances such as new antiplatelet treatments and drug eluting stents, outcomes for diabetic patients after PCI are still significantly worse than for non-diabetic patients. This article summarises what is known about the pattern and severity of diabetic coronary disease, what mechanisms are responsible for these differences, and whether this information can help explain the poorer prognosis for these patients after PCI and form the basis of interventions to improve outcome.

Objective: Previous studies have suggested that resting myocardial blood flow is within normal limits in most chronically dysfunctional left ventricular segments which improve function after coronary artery revascularisation (hibernating myocardium). The aim of this study was to assess myocardial blood flow and coronary vasodilator reserve in hibernating myocardium before and after coronary revascularisation., Patients and Methods: 30 patients with multivessel coronary disease undergoing coronary revascularisation (21 patients with bypass grafting and nine with coronary angioplasty), and 21 age and sex matched healthy volunteers (controls). Myocardial blood flow (MBF, ml/min/g) was measured by positron emission tomography using oxygen-15 water at rest and after dipyridamole (MBFdip, 0.56 mg/kg in four minutes). Coronary vasodilator reserve was calculated as MBFdip/MBF. Regional wall motion was assessed with echocardiography., Results: Before revascularisation there were 48 remote and 275 dysfunctional myocardial segments, of which 163 (59%) improved function after revascularisation (hibernating). In hibernating segments coronary vasodilator reserve before revascularisation was significantly lower than in remote segments (1.97 (0.7), p < 0.0001) and controls (3.2 (1.5), p < 0.0001). In hibernating segments, myocardial blood flow remained unchanged after revascularisation (0.94 (0.3) v 0.95 (0.3) ml/min/g, p = 0.3) while coronary vasodilator reserve increased (1. 47 (0.7) v 1.98 (1.0), p < 0.0001). Myocardial blood flow was similar in remote, hibernating segments before and after revascularisation and in controls., Conclusions: This study confirms that myocardial blood flow at rest in hibernating myocardium is within normal limits in most segments, and that hibernating myocardium is characterised by an impaired coronary vasodilator reserve which improves significantly after coronary revascularisation.

Objectives: To determine the efficacy of coronary angioplasty as the sole method of revascularisation in patients with coronary artery disease and chronically dysfunctional but viable myocardium (hibernating myocardium), and to assess the effect of restenosis on functional outcome., Design and Patients: 24 consecutive patients with hibernating myocardium were studied. Positron emission tomography was used to assess myocardial viability, blood flow, and flow reserve. One patient refused angioplasty, one had bypass surgery, and one died while waiting for an elective procedure. The procedure failed in three patients. The remaining 18 patients had repeat echocardiography, 15 had repeat coronary angiography, and nine had repeat assessments of blood flow and flow reserve at mean (SD) 17 (2) weeks after angioplasty. In three patients restenosis was documented., Results: The wall motion score index in the revascularised territories improved from 1.71 (0.37) to 1.34 (0.47) (p = 0.008). Thirty of 51 dysfunctional segments improved in territories without restenosis compared with three of 14 in restenosed territories (p = 0.001). Hibernating and normal segments had comparable flows (0.82 (0.26) v 0.89 (0.24) ml/min/g; NS) while flow reserve was lower in hibernating segments (1.55 (0.68) v 2.07 (1.08); p = 0.03). In segments without restenosis flow reserve improved from 2.03 (1.25) to 2.33 (1.4) (p = 0.03). Sensitivity, specificity, and positive and negative predictive accuracy of the viability study were 97%, 77%, 82%, and 96%, respectively. After excluding patients with restenosis, specificity and positive predictive accuracy improved to 90% and 93%., Conclusions: Angioplasty improves function in hibernating myocardium, and restenosis prevents recovery; hibernating myocardium is characterised by an impairment of flow reserve; restenosis affects the diagnostic accuracy of viability studies.

Background: Glucose-insulin-potassium (GIK) therapy has been advocated for the treatment of acute myocardial infarction. However, the results from the clinical trials have been inconclusive, largely because of the small number of patients recruited and discrepancies between protocols used in these studies., Method and Results: A systematic MEDLINE search for all the randomized placebo-controlled studies of GIK therapy in acute myocardial infarction was made, and a meta-analysis of the mortality data was performed. Fifteen trials were identified, 5 were excluded because of poor randomization, and 1 was excluded because recruitment was limited to diabetic patients. The 9 remaining trials with a total of 1932 patients were included in the analysis. Hospital mortality was reduced from 21% (205 of 972 patients) in the placebo group to 16.1% (154 of 956) in the GIK group (P=.004; odds ratio, 0.72; 95% confidence interval [CI], 0.57 to 0.90). The proportional mortality reduction was 28% (CI, 10% to 43%). The number of lives saved per 1000 patients treated was 49 (95% CI, 14 to 83)., Conclusions: The findings indicate that GIK therapy may have an important role in reducing the in-hospital mortality after acute myocardial infarction. The value of this therapy in the era of thrombolysis and acute revascularization by primary angioplasty can be fully resolved only by conducting a large randomized mortality study.

Thrombolysis in Myocardial Infarction (TIMI) flow scores were originally devised as semiquantitative angiographic measures of coronary artery perfusion. Several studies have indicated an important relation between different TIMI flow grades at 90 minutes after thrombolysis and clinical outcome. To further evaluate this relation we conducted a metaanalysis of all angiographic, postinfarction trials that studied the relation between individual 90-minute TIMI flow grades and mortality rates. In 4687 pooled patients, the mortality rate was lowest in patients with TIMI grade 3 flow (3.7%) and significantly lower than those with TIMI 2 (6.6%, p = 0.0003; odds ratio 0.55; 95% confidence interval [CI] 0.4% to 0.76%) or TIMI 0/1 flow (9.2%, p < 0.0001; odds ratio 0.38; 95% CI 0.29% to 0.5%). The mortality rate difference between TIMI grade 2 and TIMI grade 0/1 patients was also significant (p = 0.02; odds ratio 0.7; 95% CI 0.51% to 0.94%). This study confirms the importance of achieving rapid and complete reperfusion after acute myocardial infarction with the best outcome associated with 90-minute TIMI 3 flow. Furthermore, it shows that although TIMI 2 flow (partial perfusion) is not equivalent to TIMI 3 flow, it nevertheless still confers a significant survival benefit compared with TIMI flow 0/1.

Thrombolytic therapy has revolutionised the treatment of acute myocardial infarction. This has led to a need for rapid and accurate diagnosis of this condition, provision of a triage protocol to achieve initiation of thrombolytic therapy as soon as the diagnosis has been made, and knowledge of the benefit:risk ratio of thrombolytic therapy in different subgroups of patients to allow the most effective use of these agents without compromising patient safety.

Background: Angiopeptin is a cyclic octapeptide analogue of somatostatin that has been shown to limit myointimal thickening of arteries in balloon injury models and to restore the vasodilating response to acetylcholine. A randomized, double-blind placebo controlled trial was conducted to assess the effect of angiopeptin in restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA)., Methods and Results: Patients received a continuous infusion of either placebo or angiopeptin subcutaneously 6 to 24 hours before PTCA and for 4 days after PTCA (3 mg per 24 hours before PTCA followed by 6 mg per 24 hours after PTCA and for the remaining period). A 1.5-mg bolus dose of placebo or angiopeptin was given at PTCA. Aspirin (acetylsalicylic acid, 150 mg/d) was administered throughout the study period. Coronary angiograms obtained before and after PTCA and at 6-month follow-up were subjected to computerized quantification. Clinical follow-up was performed after 12 months. Primary clinical end points were death, myocardial infarction, coronary artery bypass surgery, or repeat PTCA. In total, 553 patients with 742 lesions were randomized. Clinical follow-up was available for all 553 patients. Angiopeptin decreased the clinical events during 12 months of follow-up from 36.4% in the placebo-treated group to 28.4% in the angiopeptin-treated patients (P = .046). Quantitative angiography after PTCA and at follow-up was available in 423 of 455 patients who underwent successful PTCA. The minimal lumen diameter at follow-up was 1.52 +/- 0.64 mm in the angiopeptin-treated group compared with 1.52 +/- 0.64 mm in the placebo-treated patients (P = .96). The late losses were 0.31 +/- 0.59 and 0.30 +/- 0.62 mm (P = .81) and the restenosis rates (> 50% diameter stenosis at follow-up) were 36% and 37% (P = .85) in the angiopeptin- and placebo-treated groups, respectively., Conclusions: In this study, angiopeptin significantly decreased the incidence of clinical events, principally the rate of revascularization procedures. In contrast, no significant effect was seen on angiographic variables.

There remains a need to establish adequate protocols for investigating the short- and long-term follow-up of revascularization procedures. For coronary angioplasty the most reliable basis for decision-making in managing patients is the symptomatology of the patient. For bypass surgery a protocol should be established to evaluate patients late, at 5 to 10 years following bypass surgery, in particular those with saphenous vein grafting, as graft and patient survival begins to fall after this period. Investigation after this may be too late for many patients who may already have several occluded grafts and poor left ventricular function, two of the most important prognostic factors post bypass surgery. The improvement and refinement of non-invasive investigations has led to a better understanding of the value and limitations of many of these tests, but it is particularly important that the limitations of many investigation are fully appreciated when they are used to influence clinical decisions. In this regard, a study comparing and integrating the predictive value of the persistence or return to symptoms, a positive non-invasive test, and a positive invasive test would surely prove invaluable.

During a 2-year period, 136 self-expanding Wallstents were implanted in saphenous vein bypass grafts in 69 patients with end-stage coronary artery disease. All patients had severe symptoms and the majority were poor candidates for either repeat surgery or conventional bypass coronary angioplasty because of unfavorable native anatomy, impaired left ventricular function, or a high-risk bypass lesion anatomy for coronary angioplasty. All procedures were technically successful without major complications and a need for emergency bypass surgery. However, during the hospital stay acute thrombotic complications occurred in seven patients (10%) resulting in one death and acute myocardial infarction in five patients and necessitating emergency repeat PTCA in two patients and repeat CABG in four. Twenty-three patients had serious hemorrhagic complications directly related to the rigorous anticoagulation schedule. Two patients died of fatal cerebral bleeding. During follow-up, another five patients died accounting for a total mortality rate of 12%. At late angiographic follow-up (4.9 +/- 3.4 months, n = 53), 25 patients (47%) had a restenosis (greater than or equal to 50% DS) within or immediately adjacent to the stent, necessitating reintervention in 19 patients (PTCA, n = 12; repeat CABG, n = 7). In the group without stent-related restenosis (n = 28), 15 patients had progression of disease in either the native or bypass vessels leading to recurrence of major anginal symptoms within 1 to 24 months. Ten of these patients required further intervention (stent, n = 6; PTCA, n = 3; repeat CABG, n = 1). Stenting in saphenous coronary bypass grafts can be performed safely with excellent immediate angiographic and clinical results.(ABSTRACT TRUNCATED AT 250 WORDS)

Because many ongoing clinical restenosis prevention trials are using quantitative angiography to assess whether a drug is capable of reducing the amount of intimal hyperplasia, quantitative angiographic risk factors for angiographic luminal narrowing after balloon angioplasty were determined, including stretch and elastic recoil at the dilatation site. Quantitative analysis was performed on 666 lesions in 575 patients during angioplasty and at 6-month follow-up. Stretch was defined as balloon diameter minus minimal luminal diameter (MLD) before angioplasty/reference diameter, and recoil as balloon diameter minus MLD after angioplasty/reference diameter. Multivariate analysis was used to yield independent risk factors for luminal narrowing at follow-up. Predictors of absolute change in MLD were (1) relative gain at angioplasty (gain in millimeters normalized for reference diameter) and (2) lesion length. To allow risk stratification, logistic regression analysis was applied using the decrease in MLD as a binary outcome variable. A decrease in MLD at follow-up of greater than or equal to 0.72 mm was considered significant. Variables retained in the model were: relative gain greater than 0.3 mm (rate ratio 2.9), relative gain 0.2 to 0.3 (rate ratio 2.1), stenosis length greater than or equal to 6.8 (rate ratio 1.7), and thrombus after angioplasty (rate ratio 2.6). Although stretch was significantly related to luminal narrowing at univariate analysis, it was not retained in the multivariate models. A large gain in lumen diameter at angioplasty, dilation of long lesions, and angiographically determined thrombus after angioplasty were found to be accompanied by more severe luminal narrowing at follow-up.

Restenosis after coronary angioplasty is the single complication that most limits this revascularization procedure in clinical practice. The process is largely unpredictable and the lesion-related factors predisposing to restenosis are poorly understood, with little consensus in published reports. In this study using detailed quantitative angiographic measurements to assess 490 lesions, the simple lesion characteristics associated with restenosis were defined and the relation to the restenosis process documented. Restenosis was defined as an absolute deterioration in the minimal lumen diameter by greater than or equal to 0.72 mm, a criterion based on the 95% confidence intervals for repeat angiographic measurements. This was chosen in an attempt to separate spurious changes due to a poor angiographic result and the variability of angiographic measurements from significant changes due to the restenosis process. The principal determinants of restenosis were found to be a large improvement in the minimal lumen diameter at the time of dilation (1.13 mm for the restenosis group compared with 0.86 mm for the no restenosis group [p less than 0.0001]) and an optimal postangioplasty result (minimal lumen diameter 2.28 mm in the restenosis group compared with 2.05 mm [p less than 0.001] in the no restenosis group, corresponding to a 25% and a 30% diameter stenosis, respectively [p less than 0.0001]). These observations reported for the first time suggest that the distinction needs to be made between a "clinical restenosis" of greater than or equal to 50% diameter stenosis and the "restenosis process" as measured by the absolute changes occurring during and after angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

An attempt to assess the "utility" of directional atherectomy was made using a new quantitative angiographic index. This index can be subdivided into an initial gain component and a restenosis component. The initial gain index is the ratio between the gain in diameter during intervention and the theoretically achievable gain (i.e., reference diameter). The restenosis index is the ratio between the decrease at follow-up and the initial gain during the procedure. The net result at long-term follow-up is characterized by the utility index, which is the ratio between the final gain in diameter at follow-up and what theoretically could have been achieved. For this purpose, 30 coronary artery lesions were selected from a consecutive series of successfully dilated primary angioplasty lesions and were matched with the initial 30 successfully treated primary atherectomy lesions. Matching by location of stenosis and reference diameter resulted in 2 comparable groups with identical preprocedural stenosis characteristics. Atherectomy resulted in an increase in minimal luminal diameter 2 times larger than angioplasty (1.53 vs 0.77 mm; p less than 0.0001). However, at follow-up there was a significant decrease in minimal luminal diameter and a significant increase in percent diameter stenosis in the groups with atherectomy and angioplasty (1.69 +/- 0.58 vs 1.57 +/- 0.58 mm, p = not significant [NS], and 37 +/- 18 vs 47 +/- 18%, p = NS, respectively). The decrease in minimal luminal gain was more pronounced in the group with atherectomy than in that with angioplasty (0.92 +/- 0.69 vs 0.35 +/- 0.51 mm; p = 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Intracoronary stents may be effective when used as "bail-out" devices for acute complications after percutaneous transluminal coronary angioplasty. Furthermore, preliminary reports have demonstrated some promising results with stents with regard to the reduction of restenosis. Several stent devices are available for preclinical and clinical evaluation. The use of these stainless-steel stents has been limited by poor visibility during fluoroscopy and thrombogenicity during the first days to weeks after implantation. We therefore investigated the immediate and short-term effects on arterial patency of a new, radiopaque, balloon-expandable coil stent in normal coronary arteries of pigs., Methods and Results: In 10 animals, a stent was placed in two of the three epicardial coronary arteries. During the implantation procedure, the animals received heparin; after the procedure, no antithrombotic drugs were administered. After 1 week (five animals and 10 stents) or 4 weeks (five animals and 10 stents), repeat angiography was performed, followed by pressure-fixation of the coronary arteries for light and electron microscopic examination. Angiographic analysis revealed that all stented coronary segments were patent and without signs of intraluminal defects. Scanning electron microscopy showed complete endothelial covering of all stents within 7 days. Light microscopy showed a reduced tunica media locally under the stent wires, which resulted from exerted pressure. The neointima on top of the stent wires measured 56 microns (range, 42-88 microns) after 1 week and 139 microns (range, 84-250 microns) after 4 weeks., Conclusions: Results from this study show that this radiopaque endoprosthesis can be safely placed in normal coronary arteries of pigs. After 4 weeks, all stents were patent and there was no need for additional antithrombotic treatment, whereas neointimal proliferation was limited.

Background: The placement of stents in coronary arteries after coronary angioplasty has been investigated as a way of treating abrupt coronary-artery occlusion related to the angioplasty and of reducing the late intimal hyperplasia responsible for gradual restenosis of the dilated lesion., Methods: From March 1986 to January 1988, we implanted 117 self-expanding, stainless-steel endovascular stents (Wallstent) in the native coronary arteries (94 stents) or saphenous-vein bypass grafts (23 stents) of 105 patients. Angiograms were obtained immediately before and after placement of the stent and at follow-up at least one month later (unless symptoms required angiography sooner). The mortality after one year was 7.6 percent (8 patients). Follow-up angiograms (after a mean [+/- SD] of 5.7 +/- 4.4 months) were obtained in 95 patients with 105 stents and were analyzed quantitatively by a computer-assisted system of cardiovascular angiographic analysis. The 10 patients without follow-up angiograms included 4 who died., Results: Complete occlusion occurred in 27 stents in 25 patients (24 percent); 21 occlusions were documented within the first 14 days after implantation. Overall, immediately after placement of the stent there was a significant increase in the minimal luminal diameter and a significant decrease in the percentage of the diameter with stenosis (changing from a mean [+/- SD] of 1.88 +/- 0.43 to 2.48 +/- 0.51 mm and from 37 +/- 12 to 21 +/- 10 percent, respectively; P less than 0.0001). Later, however, there was a significant decrease in the minimal luminal diameter and a significant increase in the stenosis of the segment with the stent (1.68 +/- 1.78 mm and 48 +/- 34 percent at follow-up). Significant restenosis, as indicated by a reduction of 0.72 mm in the minimal luminal diameter or by an increase in the percentage of stenosis to greater than or equal to 50 percent, occurred in 32 percent and 14 percent of patent stents, respectively., Conclusions: Early occlusion remains an important limitation of this coronary-artery stent. Even when the early effects are beneficial, there are frequently late occlusions or restenosis. The place of this form of treatment for coronary artery disease remains to be determined.

Little is known about the elastic behavior of the coronary vessel wall directly after percutaneous transluminal coronary angioplasty (PTCA). Minimal luminal cross-sectional areas of 151 successfully dilated lesions were studied in 136 patients during balloon inflation and directly after withdrawal of the balloon. The circumvent geometric assumptions about the shape of the stenosis after PTCA, a videodensitometric analysis technique was used for the assessment of vascular cross-sectional areas. Elastic recoil was defined as the difference between balloon cross-sectional area of the largest balloon used at the highest pressure and minimal luminal cross-sectional area after PTCA. Mean balloon cross-sectional area was 5.2 +/- 1.6 mm2 with a mean minimal cross-sectional area of 2.8 +/- 1.4 mm2 immediately after inflation. Oversizing of the balloon (balloon artery ratio greater than 1) led to more recoil (0.8 +/- 0.3 vs 0.6 +/- 0.3 mm, p less than 0.001), suggestive of an elastic phenomenon. A difference in recoil of the 3 main coronary branches was observed: left anterior descending artery 2.7 +/- 1.3 mm2, circumflex artery 2.3 +/- 1.2 mm2 and right coronary artery 1.9 +/- 1.5 mm2 (p less than 0.025). The difference was still statistically significant if adjusted for reference area. Thus, nearly 50% of the theoretically achievable cross-sectional area (i.e., balloon cross-sectional area) is lost shortly after balloon deflation.

Exercise electrocardiographic (ECG) testing during follow-up after coronary angioplasty is widely applied to evaluate the efficacy of angioplasty, even in asymptomatic patients. One hundred forty-one asymptomatic patients without previous myocardial infarction underwent quantitative exercise ECG testing and quantitative coronary angiography 1 to 6 months after successful angioplasty in single vessel coronary artery disease to 1) determine the value of exercise ECG testing to detect "silent" restenosis, and 2) assess the long-term prognostic value of exercise ECG testing and coronary angiography. The prevalence of restenosis (defined as greater than or equal to 50% luminal narrowing at the dilation site) was 12% in this selected study group. Of 26 patients with an abnormal exercise ECG (ST segment depression greater than or equal to 0.1 mV), only 4 (15%) showed recurrence of stenosis. Sensitivity and specificity for detection of restenosis were 24% and 82%, respectively. One hundred thirty-four patients (95%) were followed up 1 to 64 months (mean 35) after exercise ECG testing and coronary angiography. Thirty-two patients (24%) experienced a cardiac event: in 25 patients (78%) the initial event was recurrent angina pectoris (New York Heart Association class III or IV) and in 7 patients (22%) it was myocardial infarction, although cardiac death did not occur. The mean interval between exercise ECG testing and the initial cardiac events was 14 months (range 1 to 55), whereas 47% of the initial events took place less than or equal to 6 months after exercise ECG testing.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of this prospective study was to compare the incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA) in patients with stable and unstable angina before the procedure. Between January 1984 and February 1986, 344 patients with stable angina and 228 patients with unstable angina underwent PTCA. The primary success rate was 86.3 per cent in patients with stable angina (297 patients) and 87.7 per cent in patients with unstable angina (200 patients). The patients were recalled for systematic control coronary arteriography at 30, 60, 90, 120 or 150 days, and was obtained in 83.8 per cent of patients with stable angina and in 86 per cent of patients with unstable angina. The degree of stenosis before and the angiographic changes after PTCA and at control coronary arteriography were evaluated by a computer-assisted automatic contour detection system. The three criteria of restenosis were: 1) over 50 per cent loss of the benefit of PTCA, 2) residual post-PTCA stenosis increasing from less than 50 per cent to more than 50 per cent at control arteriography, 3) a decrease in the minimum intraluminal diameter of at least 0.72 mm with respect to the immediate post-PTCA result. A comparison between the two groups of patients showed that the average age was slightly greater in patients with unstable angina (56 +/- 9 years vs 58 +/- 9 years, p = 0.047). Apart from this difference, the two groups were comparable with regards to the average number of lesions dilated per patient, the date of control arteriography, the severity of the coronary artery disease and previous bypass surgery, angioplasty and infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

With the high initial success rates for coronary angioplasty that are reported regularly, it has become increasingly difficult to demonstrate methods or techniques that are able to provide more beneficial early results than can be achieved by conventional angioplasty. On the other hand, the incidence of late restenosis has remained much the same over the 10 years that angioplasty has been part of clinical practice, and there is still no proved intervention that modifies the restenosis process. Therefore, the problem of restenosis has assumed increasing relevance in determining the clinical value of coronary angioplasty and, accordingly, studies that address the problem of restenosis need to become more exacting. Although numerous articles have addressed the problem of restenosis in the clinical setting, many defining certain factors associated with restenosis and possible interventions to reduce the incidence of restenosis, there is surprisingly little consensus. Most of the discrepancies can be attributed to three factors: 1) the selection of patients, 2) the method of analysis, and 3) the definition of restenosis employed. This review shows how these three factors influence the outcome and conclusions of restenosis studies.

A 100 cm-long 16.5 F valvuloplasty catheter introducer was assessed as an adjunct for percutaneous transluminal aortic valvuloplasty (PTAV) via the femoral artery in 31 patients with severe aortic stenosis. Observed improvements in peak systolic gradient (81.6 +/- 29.9 mm Hg vs. 35.5 +/- 16.0 mm Hg, P less than 0.000001) and aortic valve area (0.6 +/- 0.4 cm2 vs. 1.0 +/- 0.6 cm2, P less than 0.00001) were similar to those achieved in a control group (C) of 17 patients in which no femoral sheath was used. However, a shorter procedure duration (211 +/- 81 min vs. 117 +/- 30 min, P less than 0.001) and a reduced rate of vascular complications at the femoral puncture site (41% vs. 6.5%) were observed in patients in whom the long sheath (LS) technique was used. The frequency of other PTAV-related complications was comparable (C = 35%, LS = 29%, P = n.s.). Other technical advantages of this device are: 1) prevention of looping and bending of the balloon catheter in tortuous vessels and easy positioning of the balloon across the aortic orifice provided by the LS trackability, 2) stabilisation of the balloon during inflation, 3) monitoring of supravalvular aortic pressure provided by the side-arm of the LS and reliable measurement of systolic gradient, and 4) the ability to perform aortograms without the need of another catheter in the ascending aorta. Thus, in our experience, the long sheath technique is a valuable adjunct for PTAV.

In order to evaluate the relation between balloon design (monofoil, trefoil) and valvular configuration, experimental aortic valvuloplasty was performed in four post-mortem hearts with calcific aortic stenosis of various morphology. The degree of obstruction of the aortic orifice was assessed by computed axial tomography during inflation of monofoil 15 and 19 mm and trefoil 3 x 12 mm balloon catheters. We also evaluated the hemodynamic repercussion of balloon inflation (fall in systolic aortic pressure) in four elderly patients with acquired aortic stenosis who underwent a percutaneous transluminal aortic balloon valvuloplasty, with stepwise increasing balloon sizes of 15 mm, 19 mm and 3 x 12 mm, as during our in vitro experiments, and who underwent aortic valve replacement later on. In these patients, we correlated the anatomy of the excised aortic valves with the retrospective analysis of aortic pressure curves recorded during previous valvuloplasty procedures. Our experimental and clinicopathological observations showed that the degree of obstruction of the aortic orifice in post-mortem specimens and the tolerance to balloon inflation in live patients are dependent of the valvular configuration. Although trefoil balloons have the theoretical advantage to avoid complete obstruction of the aortic orifice during inflation, we observed that in presence of a tricuspid configuration, they could be potentially more occlusive than monofoil balloons since each of the 3 individual components of the trefoil balloon occupied the intercommissural spaces while inflated. However, they offered more residual free space when inflated in aortic valves with a bicuspid configuration (i.e. congenitally bicuspid valves or tricuspid valves with one fused commissure). In our opinion, these observations are relevant, since degenerative disease of the aortic valve (i.e. tricuspid valve without commissural fusion) is now recognized as the most common etiology of aortic stenosis in the elderly.

Coronary angioplasty is complicated by acute occlusion (within 24 hours) and late restenosis (within 6 months) in 2-5% and 20-40% of the cases, respectively. Vascular endoprostheses (stents) may provide the cardiologist with a solution to some of these complications. Several stent-devices are now available for experimental and clinical evaluation. In this study we describe our experience with two metallic stents in normal arteries of swine. Self-expandable, stainless steel stents (3.5 mm diameter) were implanted in 17 peripheral arteries, eight of which were deendothelialized by prior balloon angioplasty. Following implantation, the animals received antithrombotic therapy with acenocoumarol and aspirin (8 stents), or aspirin alone (9 stents). After 1 week repeat angiography was performed, which showed patency of all stented arteries. Microscopy showed complete covering by neointima, 80 microns in thickness. This self-expandable stent (SES) and a balloon-expandable stent (BES), constructed of tantalum, were implanted in normal coronary arteries. SES (3.0 and 3.5 mm) receiving animals were treated with coumadines (10 stents) or received no antithrombotic treatment (16 stents) after implantation. BES receiving animals were also not treated (10 stents). Three untreated animals with SES died suddenly within 48 hours. Postmortem examination showed partial or complete thrombosis of all six stents in these animals, resulting in a patency rate of 62% after 1 week. All animals with SES, which were treated with coumadines, and all animals with BES (untreated) had patent stents after one week. It is concluded that SES implanted in normal coronary arteries of pigs, which do not receive additional antithrombotic treatment, show a 38% occlusion rate within 48 hours, but show 100% patency after 1 week, when the animals are treated with coumadines. BES implanted in normal coronary arteries of pigs, which do not receive antithrombotic drugs, are 100% patent after 1 week.

The assessment of restenosis following angioplasty has become increasingly important in determining the clinical value of the procedure. Despite this there has been no uniformly accepted methodology for assessing the procedure and consequently the published results have often been misleading with little concensus. In this paper some of the irregularities are documented and practical ways for adapting methodology proposed.

Current evidence with regard to the possible association between clinical expression of coronary disease prior to the time of angioplasty, and the subsequent risk of restenosis following successful dilatation, remains inconclusive. To prospectively compare the incidence of restenosis in stable versus unstable angina pectoris patients, follow-up angiography was performed in 85 percent of patients from a consecutive series with a successful PTCA, irrespective of presence or absence of recurrent ischemic symptoms. Furthermore, changes in lesion severity were assessed quantitatively by an automated edge-detection technique rather than visual analysis. Employing such a study design and follow-up protocol, it was found that the incidence of restenosis in patients with stable coronary artery disease was similar to that of patients with unstable rest angina, irrespective of the type of angiographic definition used.

Data from experimental, clinical, and pathologic studies have suggested that the process of restenosis begins very early after coronary angioplasty. The present study was performed to determine prospectively the incidence of restenosis with use of the four National Heart, Lung, and Blood Institute and the 50% or greater diameter stenosis criteria, as well as a criterion based on a decrease of 0.72 mm or more in minimal luminal diameter. Patients were recatheterized at 30, 60, 90, or 120 days after successful percutaneous transluminal coronary angioplasty (PTCA). After PTCA all patients received 10 mg nifedipine three to six times a day and aspirin once a day until repeat angiography. Of 400 consecutive patients in whom PTCA was successful (less than 50% diameter stenosis), 342 underwent quantitative angiographic follow-up (86%) by use of an automated edge-detection technique. A wide variation in the incidence of restenosis was found dependent on the criterion applied. The incidence of restenosis proved to be progressive to at least the third month for all except NHLBI criterion II. At 4 months a further increase in the incidence of restenosis was observed when defined as a decrease of 0.72 mm or more in minimal luminal diameter, whereas the criteria based on percentage diameter stenosis showed a variable response. The lack of overlap between the different restenosis criteria applied affirms the arbitrary nature of angiographic definitions currently in use. Restenosis should be assessed by repeat angiography, and preferably ascertained according to the change in absolute quantitative measurements of the luminal diameter.

To determine the changes in stenotic and nonstenotic segments of a dilated coronary artery, detailed quantitative angiographic measurements were performed in 342 patients (398 lesions) immediately after angioplasty and at a predetermined follow-up time of 30, 60, 90 or 120 days after the dilation. Measurements of the stenotic segments were expressed as minimal luminal diameter, and the adjacent nonstenotic segments were expressed as interpolated reference diameter (both in millimeters). A follow-up rate of 86% was achieved. In the patients followed up at 30 and 60 days, there was no significant change in either the mean minimal luminal diameter or the mean reference diameter. However, at 90 and 120 days, there was significant deterioration in both the mean minimal luminal diameter (-0.37 and -0.42 mm, respectively) and the mean reference diameter (-0.17 and -0.26 mm, respectively), all of the changes being highly significant (p less than 0.00001). The reference diameter is involved in the dilation process and may be subject to the same restenosis process that takes place in initially stenotic segments. Percent diameter stenosis measurements, which are conventionally used to express the change in the severity of a stenosis after angioplasty, will tend to underestimate the change when there is a simultaneous reduction in the reference diameter.

Eight elderly patients (mean (SD) age 72.6 (8.5) years) with severe calcified stenosis of the aortic valve were considered for transluminal balloon dilatation in the Thoraxcenter between March and November 1986. In one patient the procedure could not be performed because of technical difficulties. Balloons of increasing diameter (13-25 mm) were successively passed retrogradely from the femoral artery and manually inflated with pressures of 400-600 kPa (4-6 atmospheres). Post-dilatation, there were significant changes in left ventricular pressures (from 237/21 to 204/13 mm Hg), mean systolic gradient (from 66 to 41 mm Hg, systolic aortic flow (from 172 to 202 ml/s, and aortic valve area (from 0.47 to 0.74 cm2); the cardiac index did not increase significantly (from 2.4 to 2.5 l/min/m2). One patient developed a pseudoaneurysm at the site of the femoral artery puncture that required surgical repair two months after the procedure; one patient experienced an acute left hemianopia during the procedure but had almost completely recovered at discharge. Five patients maintained a clinical improvement at a mean follow up time of 4.5 months after the procedure; two patients underwent aortic valve replacement, one because of minimal haemodynamic improvement after aortic balloon dilatation and persistence of severe dyspnoea and the other because of late recurrence of symptoms caused by restenosis after a successful procedure. Aortic balloon dilatation provides an alternative treatment for patients who are poor surgical candidates for cardiac or extracardiac reasons. At this stage the limited haemodynamic improvements suggest that the treatment can only be regarded as palliative, although proposed technical advances may achieve better immediate results in the future. Long term follow up is needed to evaluate the usefulness of this technique.

An intraluminal stent was implanted in 5 patients after dilatation of an aorto-coronary venous graft. In the first 4 patients the procedure was motivated by restenosis after angioplasty. In the 5th patient the stent was implanted as a first-line measure in a case of dilated venous bypass stenosis. Stent implantation carries a risk of thrombosis and requires effective anticoagulation. Thus, one of our patients had to be reoperated upon for prosthetic thrombosis facilitated by the withdrawal of anticoagulants owing to a gastrointestinal haemorrhage. After a 3-month follow-up, the results seem to be encouraging in spite of a case of restenosis located at the proximal end of the tutor. However, more time will be needed to determine precisely the effectiveness of stents in the prevention of restenosis after venous graft dilatation.

To investigate the clinical usefulness of intracoronary Doppler recordings during percutaneous transluminal coronary angioplasty (PTCA), the changes of intracoronary blood flow velocity during PTCA were assessed in 20 patients with single proximal coronary stenosis, using a Doppler probe end-mounted on the tip of a PTCA catheter. A mean of 4 inflations was performed in each patient. Intracoronary velocities were measured before and after each inflation and during peak reactive hyperemia after each transluminal occlusion. Quantitative analysis of the coronary stenosis was assessed before and after PTCA, and the dilatation resulted in an increase in minimal luminal cross-sectional area from 1.1 +/- 0.8 to 2.7 +/- 1.2 mm2. A gradual and significant improvement in velocities was observed after the first 3 dilatations, but in 15 of the 20 patients the resting and hyperemic velocities were not affected by the fourth dilatation. Coronary flow reserve measured during reactive hyperemia after the last dilatation with the PTCA catheter across the lesion was 1.9. This value of coronary flow reserve is compatible with the residual stenosis measured after PTCA when corrected for the presence of the Doppler balloon catheter (0.68 mm2). This application of the Doppler technique may provide a new method of on-line functional monitoring of the PTCA procedure in individual patients, but does not yet allow an accurate prediction of the change in coronary geometry brought about by PTCA.

Twenty-five elderly patients with calcific aortic stenosis, 12 male (48%) and 13 female (52%), mean age 74.8 +/- 7.6 years, underwent percutaneous aortic balloon valvuloplasty between March 1986 and September 1987. Twenty-two patients (88%) were in class III-IV of the New York Heart Association, 13 (52%) had a history of previous angina and 7 (28%) of syncopal attacks. All patients had been considered either unsuitable or high-risk candidates for aortic-valve replacement because of age or associated diseases. Balloons of increasing size (area ranging from 1.3 to 3.8 cm2 during inflation) were successively passed retrogradely from the femoral artery and manually inflated to 3-7 atmospheres. Inflation duration ranged from 15 to 260 s (mean 40 s). Post-dilatation there were significant changes in left ventricular peak-systolic and end-diastolic pressures (P less than 0.00001 and P less than 0.01, respectively), mean systolic aortic transvalvular gradient (from 73 to 43 mmHg, P less than 0.000001), mean systolic aortic flow (from 176 to 208 ml s-1, P less than 0.0001) and aortic valve area (from 0.47 to 0.72 cm2, P less than 0.000001). Major complications included: in-hospital deaths of two patients (8%) admitted in cardiogenic shock; left haemiplegia (4%); transient haemianopia (8%); development of grade III aortic insufficiency (4%); and persistent complete atrioventricular block (4%). Complications at the puncture-site occurred in 7 patients (28%)--including two femoral pseudoaneurysms and the need for surgical removal of a balloon remnant after rupture in one patient. No local haemorrhagic complications were observed in the latter eight procedures, performed using a 16.5 French 100-cm long arterial introducer. At a mean follow-up of 13.0 +/- 5.0 months, an important functional improvement persisted in 14 patients (56%), no major changes in pre-valvuloplasty symptoms were observed in 3 patients (12%), while five patients (20%) required surgical treatment after a successful valvuloplasty because of recurrence of symptoms (late valve restenosis). Percutaneous aortic balloon valvuloplasty is a possible palliative therapy in elderly patients with calcific aortic stenosis. However, its inherent immediate risk, limited haemodynamic result and the possible development of valve restenosis at medium-term follow-up, suggest that the application of this technique should be limited to poor surgical candidates.

Coronary restenosis occurs fairly early after transluminal coronary angioplasty, as suggested by anatomico-clinical, isotopic and angiographic studies. Its incidence, as reported in the literature, varies according to the clinical selection of patients, to the number of patients with follow-up angiography and the timing of this procedure, and to the criteria used to define restenosis. In this prospective study we endeavoured to determine the exact date at which restenosis takes place, as well as its true incidence, by means of 6 different angiographic criteria. The population studied was divided into five groups and each group underwent coronary arteriography at a different date: during the 1st, 2nd, 3rd, 4th and 5th post-angioplasty months respectively. In 424 of the 500 patients thus examined (84.8 p. 100), coronary angiography involved automatic detection of contours and made quantitative analysis possible. Coronary restenosis was found to occur early, with a peak of incidence in the 3rd month. Its incidence varied considerably depending on the criterion used. A critical analysis of the data has prompted us to use a criterion based on absolute values determined by quantitative angiographic analysis.

Animal studies have demonstrated that synchronised coronary sinus retroperfusion with arterial blood can provide effective perfusion of ischaemic myocardium. Preliminary clinical studies have shown that the technique can also be used with safety in human beings, and in the present study its effectiveness was assessed in three patients undergoing repeated coronary artery occlusions during percutaneous transluminal coronary angioplasty. Arterial blood was removed via an 8F catheter positioned in the femoral artery and delivered by a retroperfusion pumping system to a 7F retroperfusion balloon catheter positioned in the anterior cardiac vein. Ischaemia-related indices were monitored both before and during coronary sinus retroperfusion. These indices included high fidelity left ventricular pressure recordings and pressure derived indices (including velocities of isovolumic contraction and relaxation), as well as electrocardiographic changes and symptoms. Analysis of these variables showed that the ischaemic changes induced during coronary artery occlusion were not prevented by this type of coronary sinus retroperfusion. There was no major complication in any of the patients. It may be that adaptation of the technique or the use of alternative end points will establish a benefit, but further modifications of the delivery system are necessary for effective clinical use.

The first 840 consecutive patients who underwent percutaneous transluminal coronary angioplasty (PTCA) performed in the same institution were retrospectively assessed at an average follow-up period of 25 months after the initial procedure. The study population consisted of 506 patients with stable angina pectoris (group 1) and 334 patients with unstable angina pectoris (group 2). Clinical end points were death, nonfatal myocardial infarction, recurrent angina pectoris necessitating bypass surgery or repeat PTCA, and event-free survival. The two groups were comparable with respect to age, sex, previous myocardial infarction, ejection fraction, and number of diseased vessels. PTCA was successful in 83.0% of group 1 and 87.1% of group 2. Follow-up rates were expressed as events per attempted PTCA in a patient group. No difference in survival was observed between the two groups, the mortality rate being approximately 2.8% at 25 months. In the group with stable angina pectoris there was a lower incidence of nonfatal myocardial infarction within the first 24 hours after angioplasty; 4.3% vs 9.0% (p less than 0.01). During long-term follow-up the increase in the incidence of nonfatal myocardial infarction was similar, resulting in an overall long-term follow-up infarction rate of 8.3% and 14.2%, respectively (p less than 0.01). A higher event-free survival was observed in group 1 within 24 hours after PTCA: 93.7% vs 84.2% (p less than 0.01). During subsequent follow-up the difference in event-free survival between the two groups was no longer significant: 68.5% vs 61.2%.(ABSTRACT TRUNCATED AT 250 WORDS)